The present invention is in the field of biotechnology and specifically relates to the field of breast assessment and breast cancer screening in women.
For well over twenty years, thermometric assessment of the human female breast surface has been under investigation as a tool in the armamentarium of those concerned with the detection and treatment of breast cancer.
GB 1,490,803 (expired) and U.S. Pat. No. 4,055,166 (expired), both granted to Simpson and Green and of substantially identical content, describe a garment which is a brassiere upon and within which is mounted a plurality of sensors for the purpose of measuring breast temperature over the menstrual cyde. They referred to a menstrual cycle of breast heat amounting to a variation in surface temperature of about 1xc2x0 C. which is maximal about three days before the onset of menstruation. In the preamble, it is made clear that the intention is to detect the presence of actual cancers based on the observation that areas adjacent to a cancerous growth may be xe2x80x9cslightly warmer (say 1 or 2xc2x0 F.) than unaffected areas of the other breastxe2x80x9d and that comparison of the 24 hour temperature variation (circadian variation) between normal and cancerous breasts have shown clear differences in time structure.
In a subsequently abandoned application publication number GB 2,203,250 A, Simpson again teaches a garment in the form of a brassiere with a miniaturized electronic heat measuring device which has a number of cup temperature sensors. In a further embodiment there is disclosed another brassiere xe2x80x9chaving a single sensor net of high thermal conductivity wire centered on the nipple and extending for a few centimeters around each nipplexe2x80x9d.
In these disclosures Simpson and his colleagues make an important structural distinction between their brassiere device and the earlier breast surface measurements which had been made in hospital environments with sensors fixed on the skin. They taught the provision of a garment which would allow temperature measurements to be recorded over relatively long periods while the subject lives normally. They provide xe2x80x9capparatus for measuring surface temperatures at points in the region of the human body, including a garment having a plurality of temperature sensors located therein at spaced apart positions, and means for so storing signals representing output signals from the sensors that the relationship of each signal time of occurrence can be retrievedxe2x80x9d.
In particular, they indicate a preference for the storage means to be mounted on the garment. According to claim 1 of U.S. Pat. No. 4,055,166, the garment and the means for storing signals are integral. In Claim 1 of GB 1,490,803, the apparatus includes a garment and Claim 4, as well as other various other dependent Claims, describes a brassiere which includes sampling and storage means being integral with the brassiere.
Simpson and Green make it clear that, in relation to measurements of temperature on the breasts, the garment may be a brassiere. They teach a brassiere for measuring surface temperatures of the breasts at predetermined points, including a plurality of temperature sensors positioned in each cup of the brassiere, the sampling and storage means being integral with the brassiere.
Their underlying contention is that xe2x80x9cThe circadian rhythm of breast temperature is regarded as a normal feature of the mammary tissue differentiationxe2x80x94a response possibly of a target organ to tides of hormones in the circulation (e.g., 24-h variations in prolactin; menstrual variations in oestrogen). Consequently alterations of the circadian rhythm characteristics occur in breast pathology of which cancer is one example. In this situation the rhythm is sometimes absent and often of altered level and phase. It follows that monitoring breast temperature rhythm over daily and perhaps monthly intervals will be valuable in detection and characterization of disease, e.g. cancer.xe2x80x9d From this, and other statements in the specification, it is clear that these authors did not contemplate the application of their invention in the assessment of the future risk of developing cancer and that it was limited to detection of and characterizations of actual lesions.
The Simpson and Green patents teach a brassiere fitted with temperature sensors positioned at points where tumors have been shown to occur most frequentlyxe2x80x94at the one, two and three o""clock positions, over the nipple, and at the nine o""clock position on the left breast, and on the right breast there is a similar disposition of sensors over the upper outer quadrant, that is at nine, ten and eleven o""clock positions with a sensor over the nipple and one at the three o""clock position. They do contemplate different positioning of the sensors and that a different number may be deployed.
What is quite clear, however, is that their device, as described, is a garment fitted with temperature sensors and having means for storing signals from the sensors included with or integral with the garment. It is also quite clear from the detailed descriptions and claims that, when the apparatus is to be used on the human breast, the garment is to be a brassiere. They also clearly describe, in Claim 6 of each patent, the use of a heat shield to prevent outward heat flow through the sensor.
Simpson has since suggested that the device, which is the subject of the test described in the two patents, is subject to xe2x80x98noisexe2x80x99 and that this is due to other vasomotor phenomena. He has suggested that xe2x80x9cThe problem with the method is not the signal, but the noise from these sources.xe2x80x9d Sir James Young Simpson Memorial Lecture, J. R. Coll. Surg. Edinb., 41, June 1996. He goes on to suggest that future developments could include Doppler ultrasonography applied to the internal mammary artery and volumetric analysis of the breast and its component tissue using magnetic resonance imaging.
In the source quoted above, Simpson makes it clear that his developments are nowadays directed at trying to predict, from temperature measurements, which breasts may develop cancer later.
Although Simpson and Green appear possibly to have been the first workers to make serious attempts at detecting breast cancer by observing breast surface temperatures, theirs is not the only work. Detectors for actual cancer lesions based on breast surface temperature are still being developed and this is somewhat surprising since most authorities believe that tumors large enough to find by this method are already likely to have progressed so far as to carry with them fatal consequences.
One example is BreastAssure(trademark) made in the USA by HumaScan Inc of Cranford, N.J. The makers claim that this device is the subject of two US patents which expired on May 22nd 1998 and a Canadian patent which expired on Aug. 24th 1999; these are all believed to be to Z. L. Sagi. Financial literature on the company states the product xe2x80x9c . . . consists of a pair of mirror-image, non-invasive, lightweight, disposable soft pads, each of which has three wafer-thin segments containing columns of heat sensitive chemical sensor dots that change color from blue to pink reflecting an 8.5xc2x0 temperature range from 90xc2x0 to 98.5xc2x0 F. When placed over a woman""s breasts, inside her brassiere for a period of 15 minutes, the device registers skin temperature variations due to heat conducted from within the breast tissue to the surface of the skin. By comparing the mirror-image temperature differences between the two breasts registered by the device, the physician can objectively quantify if there is abnormal unilateral breast thermal activity, which is considered significant if there is a 2xc2x0 F. or more temperature difference between each breast in the same mirror-image location. Based on clinical studies at major medical centers, the threshold tumor size that resulted in significant skin temperature differences detectable with the device was as small as 5 mm in size.xe2x80x9d It may be worth noting that, according to some authorities, cancers of this size may well have already metastasized. Other experts to whom we have spoken doubt whether 15 minutes is an adequate time for any device placed on or over the breasts to equilibrate with breast temperature on a consistently reliable basis.
This manufacturer claims that, according to industry sources, the majority of breast tumors are, on average, at least 15 mm or larger before they are palpable by most experienced clinicians. Literature which we have seen suggests that 15-20 mm is the range in which most become tumors become palpable.
We subsequently obtained copies of a series of patents to Sagi, namely U.S. Pat. No. 4,190,058 and U.S. Pat. No. Re. 32000; U.S. Pat. No. 4,624,264 and U.S. Pat. No. 4,651,749. Generally these describe patches intended to aid in early detection of breast cancer based on thermography. The patches are substantially circular and comprise radially arranged strips of liquid crystal temperature indicators deposited upon a plurality of segments made of aluminum foil. No means are provided for measurement or display of actual temperatures and the patches are examined for areas of color change. The patches must be used with a brassiere. It is clear that the information which such a device could provide would be very limited and would, in addition, need a skilled physician in attendance to interpret the patches upon removal.
The solid metallic foil of these patches, especially when mounted on a support surface, is unlikely to conform reliably to the concavo-convex three-dimensional architecture of the human breasts and, as hereinafter described in relation to the Simpson device, this would result in non-contact regions. In the case of the Sagi device such an eventuality would lead to incorrect thermographic patterns and misinterpretation. In addition the device requires to be supplied in a multiplicity of sizes to accommodate the wide variation in breast sizes.
Another participant in this field is Biofield Inc of Roswell, Ga., USA, with its ALEXA(trademark) 1000 system. According to material released by the company onto the Internet, this employs single-use sensors and a measurement device to analyze changes in cellular electrical charge distributions associated with the development of epithelial cancers such as breast cancer. Sensors are arranged on the skin surface in and around the quadrant of the breast where a suspicious lesion has been identified and in corresponding locations on the asymptomatic breast. Sensor readings are measured and analyzed using a pre-programmed algorithm. The technology is claimed to be based on the observation that epithelial cancers are characterized by uncontrolled recurrent cell proliferation of rapid cell division. As these cells divide, an electrical charge is released. This results in a disruption, or depolarization, of the charge distribution found in normal epithelial tissue. Moreover, the depolarization appears to be progressive as cell transformation and carcinogenesis occur. It is claimed that this depolarization is measurable at the skin surface in the form of electrophysiological differentials. The final output is a single numerical and objective value, from one to thirty. The result of this test is claimed to provide an indication of the proliferation level, which is related to the probability as to whether a lesion is malignant or benign. The manufacturer claims that a task force sponsored by the European School of Oncology has reported on the measurement of electropotentials from the breast as a possible method of detecting breast cancer. This report summarizes the background and early results and suggest that this technique may have a role in the diagnosis of both palpable and non-palpable breast lesions. U.S. Pat. Nos. 5,427,098; 5,560,357; 5,415,164; 5,217,014; 5,320,101 and 5,099,844 all appear to relate to this technology. We were unable to verify these claims from enquiries made with the European Institute of Oncology, which was the initial assessment center for the original embodiment of the instant invention.
Lifeline BioTechnologies Inc, another US company, has two products which are claimed to increase the chance of finding potential breast cancers at an early stage. The KELLY MONITOR is a detection aid for early breast cancer apparently intended for use as a non-invasive complement to mammography. It consists of sensors and a small portable data storage unit, worn for up to forty-eight hours in order to capture temperature patterns which are stored for later analysis. The device dynamically monitors the physiologic activity of the breast by means of circadian rhythm analysis. This monitor uses a sixteen sensor array: seven for each breast, one for the stemum, and one to measure ambient temperature and, like the Simpson and Green disclosure, calls for placement determined by occurrence data for breast cancer. This product uses a proprietary template for identical placement on each breast. The manufacturer""s literature claims to use sensors which are considered xe2x80x9cinterchangeablexe2x80x9d, eliminating the need for insulation, adjustable resistors and continued calibration. This commercial claim appears to be directed in a negative manner at the Chronobra(trademark), a device based on Simpson and Green""s patents which does require the use of calibration and trimming resistors. It is not clear whether this product is the subject of either an issued patent or a patent application.
Unlike the other devices and products hereinbefore described, the FIRST WARNING(trademark) product is claimed to identify women who will eventually develop breast cancer and be a xe2x80x98Risk-Markerxe2x80x99. The literature indicates that, during the test, a custom-designed breast temperature sensor is integrated into a cup insert for use with the patient""s brassiere, and she will be directed to place the sensors directly within her brassiere and thus on her breast. The patient would be required to wear the device for ninety minutes each night. The sensor is intended to measure surface temperature over the breast area for each breast throughout this period. The inserts are apparently presented in several sizes to fit the wide variation in breast sizes in the female population. According to the literature, each sensor will detect the unique temperature patterns of the breast. The sensors are described as connected to a miniature storage device which is worn concealed under the clothing. The literature indicates that, at the conclusion of the test, the device is plugged into a data storage unit which is small enough to be placed on a bedside table. The data are transferred to the base and the portable unit is recharged. An additional requirement described is for a sample of saliva to be taken on a daily basis. The saliva is placed in a small vial and stored in a refrigerator in a special calendar/date related container until the test concludes. The entire test lasts for thirty days. The results are then analyzed using proprietary techniques to assess the risk factor for the patient. The company claims that traditional statistical techniques are not accurate enough in their discrimination of the data. The ultimate result is an indication of high or low risk. The product is believed to the subject of a U.S. patent application.
The practicality of this test seems to be questionable at least. It has to be done over thirty days and thus requires an enormous level of compliance in today""s fast-moving world where many women do not have well ordered lives which allow them to be constantly at home. This test also has to be done for ninety minutes each night, followed by a procedure to recharge the monitor; it is surely rather likely that the subject would fall asleep. The most limiting factor, however, is likely to be the sheer cost of thirty hormonal assays for each subject. On top of this is the question of available laboratory capacity to carry out the testsxe2x80x94on the basis of the manufacturer""s own figures, they hope to generate a level of business per xe2x80x98developing family practicexe2x80x99 which would produce a laboratory load of 3,100 hormone assays.
With the exception of the last product described, all the commercial prior art items which we have found may be called xe2x80x98breast cancer detection aidsxe2x80x99. As such,their use is limited, since any patient who already has cancer has a reduced risk of survival and a certainty of morbidity. On the other hand, any subject who tests negative, is only negative on the day of the test a nd ha s no idea of her future risk status.
In addition to the commercial items, immediately hereinbefore described, we have now become aware of a number of other patents which are considered relevant. We do not know if any of these disclosures have been commercialized.
U.S. Pat. No. 3,830,224, to Vanzetti et al, discloses means for detecting changes in temperature of the skin incorporating a plurality of multi layer packages comprising liquid crystals. No means for direct or relative measurement of temperatures is disclosed and the authors suggest that physiological phenomena such as ovulation or the presence of malignancy can be revealed by color differences between adjacent packages.
U.S. Pat. No. 3,847,139, to Flam, discloses another liquid crystal device, in this case the liquid crystal system is carried upon a fabric or textile made up into a garment worn between the neck and the waist, including the breast area. As with the Vanzetti et al patent, there is no means for direct or relative measurement of temperatures disclosed.
U.S. Pat. No. 4,522,778, to Brown, Jr. et al, shares with Flam the use of a cholesteric liquid crystal display which visually indicates areas of differential temperature with a chromatic display. Although color differentiated thermograms are generated, it is necessary to insert a strip thermometer between the device and the screen in order to measure actual skin temperatures. The thermograms must be traced by hand. As disclosed, both in the text of the specification and in the accompanying figures, it seems very unlikely that the breast scanning pad of the system could conform to the complex contours of the human breast which is necessary to ensure uniform contact. Similarly, it seems equally unlikely that this pre-requisite would be significantly assisted by an overlay web described as plastics such as polyvinyl chloride or polypropylene.
In U.S. Pat. No. 6,086,247, to von Hollen, there is disclosed a mushroom-like shaped pad. Despite the author""s reservations concerning adhesive pads expressed in his discussion of the background, the disclosure calls for just such an adhesive arrangement. In addition, this patent calls for a device in multiple sizes whereas again, in the background to the invention, the inventor refers to this feature, in relation to the Sagi patents, as a limitation with regard to those disclosures. In any event, the device, as described with reference to a preferred embodiment, requires the close involvement of a skilled third party to fit, remove the device and to read and interpret color changes in the sensors. This is another liquid crystal device with no direct or relative temperature measurements. In common with all liquid crystal display devices, there is ample evidence that such devices are not sufficiently sensitive to detect the very small fluctuations in breast temperatures which may be crucial to useful breast assessment.
U.S. Pat. No. 6,077,228, to Schonberger, is directed to the detection of actual breast tumors which, by virtue of having developed a blood supply as a result of angiogenesis, are claimed to act as heat sinks leading to differential cooling when the breasts of a subject are iced. Structurally and morphologically, the device has similarities to the Sagi disclosures of a patch and to the von Hollen disclosure in that all are intended to cover most of the breast. In the case of the Schonberger device, it seems likely that compliance might be a significant issue since subjects are required to have their breasts iced during the test.
U.S. Pat. No. 5,999,843, to Anbar, is concerned with detection of actual breast cancer using what the author calls Dynamic Area Telethermometry and infra-red imaging. Anbar states that xe2x80x9cunlike classical, thermography of the breast, the DAT test does not use the absolute temperature or temperature differences as the diagnostic parameterxe2x80x9d. This is in marked contradistinction to the instant invention hereinafter described.
U.S. Pat. No. 5,941,832 to Tumey et al and U.S. Pat. No. 5,301,681 to DeBan et al; are structurally substantially identical and share mostly the same inventor group. In FIG. 1 of both patents there is illustrated a template with four arms, each of which is adapted by the provision of a series of holes. The arms extend radially outwardly from a central portion and the template is of a sufficient size to accommodate numerous breast sizes. The central portion has an opening which is placed over the nipple to position the template and from both disclosures it is dear that the authors are teaching a template for marking purposes. Once the desired positions have been marked, the template is discarded and sensors, preferably thermistors, are adhesively attached directly to the breast skin of the subject. Signals from the sensors are used in conjunction with a neural network. The limitations of adhesively attached sensors on the human breast, particularly in regard to acceptability and compliance have been rehearsed hereinbefore with respect to various patents.
U.S. Pat. No. 3,960,138, to Doss et al, requires a thermally conductive sensor pad placed in the interior of breast receiving cups of a brassiere in good thermal contact with the wearers flesh. The requirement to use a brassiere is similar to that of the Simpson patents, as are the limitations. In this patent a thermistor is attached to each pad and forms part of a Wheatstone Bridge circuit. Temperature differences between sensor pads unbalance the bridge circuit.
U.S. Pat. No. 5,830,159, to Netta, is another brassiere-based device which the inventor calls a flat tell mammogram. It has a temperature sensor in each cup. The device also includes a pair of strain gauges each coupled to an associated cup of the brassiere. Such coupling is preferably afforded adjacent a central extent of the bottom edge thereof. In operation, each strain gauge is adapted to emit a pressure signal representative of a current pressure that is exerted by the breast on the associated cup. Such pressure is a direct function of the size of the breast. It should be noted that more than one temperature and pressure sensor may be coupled to each cup of the brassiere for providing a more accurate indication of the temperature and size of various areas of the breast.
A PCT patent application PCT/US90/02203 by Bio-Monitor Inc is published as WO 90/13092 and indicates that the inventor was Gautherie. The publication discloses a method and apparatus for analyzing information gathered from symmetric areas of a living organism. Recorded data are transmitted over a communications link to a remote data analysis center and ipsilateral and contralateral comparisons of selected temperature data are made along with a chronobiologic analysis of the temperature data. Although Gautherie did not restrict his disclosure to temperature measurement, this application is discussed and FIG. 1 and the supporting text illustrate a plurality of sensors, directly affixed to the breasts, including on the nipple/areolar area, with adhesive pads. These are connected with wires to a data collection device worn on a waist band or belt.
Gautherie makes no disclosure concerning a structure for control of the ten wires between the points of attachment on the breasts and his data acquisition device. This is particularly surprising since he states, on Page 7, that temperature data is recorded every five minutes over a twenty-four hour interval under ambulatory conditions. With multiple unconstrained wires, it is not realistic to confidently expect that all sensors would remain attached, for instance during sleep periods, even if a brassiere were to be used. There is no disclosure on the type of sensors nor the calibration thereof.
A further serious concern is that although Gautherie describes how data from the subject-worn acquisition device would be transferred to the remote analysis center, the crucial issue of secure attachment of subject identity to data is entirely in the hands of an operator with the attendant risk of disastrous human error. Such an event could lead to a sick patient being declared healthy and subsequently dying and a healthy subject being possibly subjected to disfiguring and inappropriate surgery.
A search conducted in October 2000 using the public resources of the European Patent Office did not reveal any issued patent to Gautherie or BioMonitor Inc on this or any related subject. It was also not possible to find any reference to BioMonitor Inc on the internet.
U.S. Pat. No. 5,813,400, to Devlin et al, is concerned with a connector connected to an electrode set and another connector connected to a patient monitor. Each electrode element of the connector is exclusively coded to identify it to the monitor. Such a solution would be useful in systems where a non permanent hard-wired connection between sensors and a monitor is possible or, optionally, disconnectable means would be desirable, such as where a monitor does not provide specific channel to specific sensor functions, such as calibration. The invention appears to be directed towards ensuring correct spatial configuration of electrodes particularly for purposes of EEG and EKG monitoring.
Work published by Simpson and others, well after the date of his patents, includes comparative microscopy data in cancer-associated breasts and age-matched normal breasts showing a gross excess of focal hyperplasias in pre-menopausal cancer-associated breast tissue. Additionally, epidemiological data are consistent with this finding in that such tissue is subject to a six-fold increased risk of further primary carcinogenesis. In addition, it is now known that premenopausal mammary tissue goes into a monthly pregnancy rehearsal with glandular proliferation and increased blood supply. These phenomena have been shown to produce a luteal heat cycle which produces a variation in breast surface temperature of about 1xc2x0 C. in normal women (probably not at risk of cancer). Women with cancer-associated breasts exhibit only up to about half this amplitude. The pattern of temperature rise is also different insofar as the temperature rise curve in cancer-associated breasts is relatively steady and peaks earlier in the menstrual cycle than in normals. Normals exhibit a high correlation with and dependence upon endogenous progesterone levels during the luteal phase.
The differences in breast temperatures between xe2x80x98normalxe2x80x99 women and clinically normal women with cancer-associated breasts, measured during the luteal heat cycle, are maximal during the few days just after ovulation. Breast temperature variations may be associated, at least in part, with abnormal breast arterial blood flows at particular phases of the menstrual cycle. Significantly increased blood flow commences at the start of the luteal phase, some fourteen days prior to menses. The blood supply of the breast is from the axillary artery via the lateral thoracic and acromio-thoracic branches and also from the internal mammary (thoracic) artery via its perforating branches. In the female, the branches of the second, third and fourth intercostal spaces give branches to the breast which vary in size under hormonal bombardment. Thus, although the contribution to overall elevation in breast temperature may be greater by some arteries than others, all exhibit a menstrual cycle of breast blood flow and all contribute to the breast luteal heat cycle.
In any system or device for breast surface temperature measurement which is to have broad applicability for mass screening of populations, great attention has to be given to practicability. Any such entity which consumes large amounts of time in setting up will be unacceptable.
For this reason, the physical attachment of sensors to the breast surface of subjects has not proven popular. The need to apply each sensor separately, usually with adhesive tape, is not only time consuming but has obvious disadvantages for the subject at the time of removal. There is also the problem of ensuring that individual sensors do not become detached as a result of traction on cable connecting means employed to deliver the signal to whatever means is employed for temperature data collection.
The use of a sensor array, integral with a brassiere (this garment also having means for carrying a data-logging device) is, apparently, the preferred implementation of the Simpson and Green utilities. This device, which was never supplied commercially, had the name Chronobra(trademark) and Simpson has published on this in the lay press as recently as September 1997. It is clear from other publications on this device that, although it has some functionality, there are inherent problems of poor signal, intermittent signal and sometimes a complete absence of signal, logged from certain individual sensors suggesting poor and inconsistent contact between these and the breast surface.
Analysis of the device, an example of which we obtained, suggested that the problems were unlikely to be truly electrical but are related to the structure and mechanics of the device. The manner in which thermal sensors and the garment are integrated involves the use of a sewn-in lining pad made of stiff material and provided with a plurality of perforations. A plurality of thermal sensors is each encapsulated within in a thick molding of silicone material which is in the shape of a cylindrical plug which is xe2x80x98Txe2x80x99 shaped in cross-section, each sensor being located in the xe2x80x98legxe2x80x99 of a xe2x80x98Txe2x80x99. The sensor moldings are disposed between the perforated lining pads and the cups of the brassiere. Each perforation in the lining pad accommodates the leg portion of one thermal sensor molding so as to present it to the breast surface.
We measured the thickness of the silicone mold material disposed about a number of sensors and in no case was this less than 2.0 mm. However, the least thickness measured at the end of a molding over that surface of the sensor directed towards the breast was 3.1 mm and in some cases over 4.0 mm. Since silicone rubbers are highly effective insulating materials with poor thermal conductivity, it is certain that this arrangement would lead to reduced effectiveness and possibly to repeated low readings. Simpson and Green""s disclosures call for insulating means to prevent heat loss and this may be why they employed a large plug of the selected material behind the sensors.
However, to employ such a material over the face of the active thermal sensing element suggests a fundamental misunderstanding of the principal aim at hand, which is the measurement of small variations in temperature of a target in an ambient environment, the temperature of which is not vastly different from the target itself.
Under these circumstances, the principal aim is only likely to be met either when there is no barrier at all or, if there is one, it has high thermal conductivity and is of minimal thickness.
Further analysis of the subject Chronobra(trademark) device, both on and off subjects, suggests other reasons why instances of intermittent or absent signal are encountered. First, the integral construction of the sensor array and brassiere called for by the Simpson and Green patents and embodied in the use of a lining pad, leads to a rather rigid cup construction which resembles a rounded modified cone. In most women, the breast surface is profoundly convex on the lower aspect and somewhat concave on the superior aspect. Such a mis-match of profiles explains why, in a number of cases, the sensor moldings of the upper aspect of the cups do not come into contact with the superior aspect of the breast surface at all.
Such a brassiere must, of course, be available in all rational sizes if a general population is to be tested. This inevitably increases the cost and level of inconvenience associated with this test and many others in the prior art.
Mounting the data-logging device on the brassierexe2x80x94which reads for the Simpson and Green patentsxe2x80x94between and below the cups, introduces traction on the brassiere and exacerbates the non-contact problem by pulling the upper surfaces of the cups away from the superior aspect of the breast surfaces. Each fine, twisted pair of sensor connecting leads extends from the sensor to the data-logging device separately and without further protection. This not only makes for an untidy appearance but also increases the risk of tangling and traction on individual sensors. Finally, this device does not use any form of true calibration and therefore it cannot be argued that the output from the sensors represents accurately any particular absolute temperature.
Despite a prolific prior art, it appears that a number of crucial factors have not been addressed in the collection of physiological signals from the surface of the human breast, particularly when it is the intention to apply any given solution to a large population.
First of all, no solutions in the prior art appear to deal adequately with the crucial issues of the subject interface. Any workable solution for mass application must meet the following requirements in this area:
1. Provide intimate and continuous contact, throughout any data collection period, between that part of the subject breast surface which is to be monitored and sensor means provided for the purpose of collecting the target physiological signals.
This is crucial since, if the subject interface is intermittent, collection of data will also be intermittent and may be useless. This, in turn, represents a waste of limited screening resources, a waste of the subject""s time and also, quite possibly, increased stress;
2. Provide sensor means which are capable of reliably and accurately registering very small differences in absolute signal values.
This is crucial with respect to breast surface temperature signals since, as hereinbefore discussed, women with cancer-associated breasts may exhibit temperature variations of only up to about 0.5xc2x0 C. and, in this context, sensors which measure absolute values with a sensitivity of at least 0.1xc2x0 C., and preferably considerably greater sensitivity, are clearly necessary. This applies even if only inter-sensor relative values are required to be elaborated or interpreted post data collection;
3. Present no material physical or thermal barrier between the breast surface and the sensor means in order to ensure that signal attenuation does not occur.
As immediately hereinbefore discussed, variations in physiological signals, particularly breast surface temperature signals, may be of very low amplitude and place high demands on sensor means. Any physical or thermal barrier interposed between the target and the sensor could produce a thermal gradient leading to the collection of incorrect data which could, in turn, lead to an incorrect and potentially dangerous interpretation;
4. Provide an interface which does not intrinsically limit compliance with or management of the data collection process.
This is crucial because, notwithstanding the great threat which most women perceive breast cancer to be, they will not, on a population-wide basis, accept screening methods which are painful, cause loss of dignity, are overly time consuming, compromise hygiene or are clearly unreliable. Similarly, health care and diagnostic service providers will not implement screening programs which introduce tasks or functions, other than the screening process itself, which do not form part of the organization""s core activities. Thus, solutions which require fixing of sensors directly to the breasts with adhesives, especially for long periods, are unlikely to be acceptable to the majority of women. Similarly, those solutions which require very many sizes of brassieres, whether dedicated to a particular test or general purpose, are unlikely to be acceptable to the majority of service providers since they introduce a manpower and cost requirement in respect of laundry or other cleaning means, together with extended inventory control.
Secondly, few solutions in the prior art appear to deal, at all, with the crucial issue of the integrity of measurements to be made by the sensor means. Those that doxe2x80x94Simpson and DeBan/Tumeyxe2x80x94use an algorithm method for calibration of sensor means which, by itself, may not be safe when it is considered that the level of accuracy required for thermometric measurements, in the context of breast cancer diagnosis or risk, is measurement to better than 0.1xc2x0 C.
Thirdly, none of the solutions in the prior art appear to disclose safe means for or to deal adequately with the crucial issue of ensuring that a unique identity of the subject is non-detachably linked to data collected from that subject in order to eliminate human error at the time collected data are transferred between a subject interface and any other storage or elaboration point. Furthermore, none of the prior art solutions addresses the issue of non-detachably linking the identities of any persons involved in attaching or detaching the subject interface, initiating or ending the collection of data, transferring or interpreting data or holding overall responsibility for the screening process and its consequences. Considering the importance and potentially life-threatening consequences of errors in this context, this seems remarkable.
Overall, the prior art teaches towards the desirability of a convenient method for breast screening based on thermometric data. However, none of the references we have been able to find, whether considered alone or jointly, teach a solution which is accurate, safe, acceptable and workable at both the subject and provider levels.
Since most authorities now accept that about one in twelve women in Europe and maybe as many as one in ten in the USA, dies from breast cancer and up to one in eight may develop the disease at some point in their lives, it would clearly be of enormous benefit to be able to identify which women are at risk and which are not. By such a means of risk-assessment, very great relief from stress could be imparted to the majority of women. Even women found to be at risk would be much better off since the health care system, whether public or private insurance based, would be able to release funds to enhance their surveillance, implement better avoidance strategies (perhaps involving diet and nutritional supplementation) and treat them better, should the disease eventually supervene. We estimate that in the U.K. alone, having an effective means for positively identifying those who are at risk and three quarters of those who are not at risk, would save £1.8 billion (US$ 2.7 billion) per annum, as well as avoiding a vast amount of human misery.
Clearly, there is room for substantial improvement in the management of breast cancer since the long term survival prospects, following diagnosis, are still not very encouraging, barely exceeding 50%. Mass campaigns directed at self-examination are not very successful since, even when regularly practised, women who find lumps which turn out to be malignant upon biopsy, generally detect these at a size which is lethal. This is particularly so in young women with dense breast tissue.
It may be that today""s limited success in treating this disease is partly due to the failure to recognize pre-cancerous states in mammary tissue as a whole. The investigation, observation and tracking of these states would allow earlier diagnosis and would also permit potential intervention strategies to be exploited, perhaps with marked effects on ultimate survival rates.
Other documents considered relevant are:
Gautherie, M and Gros, C M, xe2x80x9cBreast thermography and cancer risk predictionxe2x80x9d, 45: 51-56, 1980.
Simpson, H W and Griffiths, K. xe2x80x9cThe diagnosis of breast pre-cancer by the Chronobraxe2x80x9d, Chronobiology International Vol. 6, No. 4: 355-393, 1989.
Simpson, H W et al., xe2x80x9cThe luteal heat cycle of the breast in healthxe2x80x9d, Breast Cancer Research and Treatment, 27: 239-45, 1993.
Simpson, H W et al., xe2x80x9cA non-invasive test for the pre-cancerous breastxe2x80x9d, Eur. J. Cancer, Vol 31A, No. 11: 1768-1772, 1995.
Simpson, H W et al., xe2x80x9cThe luteal heat cycle of the breast in diseasexe2x80x9d, Breast Cancer Research and Treatment, 37: 169-178, 1996.
Simpson, H W. Sir James Young Simpson, Memorial Lecture 1995: xe2x80x9cBreast cancer prevention: a pathologists approachxe2x80x9d, J. R. Coll. Surg. Edinb., 41, 359-366 December 1996.
Simpson, H W et al., xe2x80x9cA clinical test for breast pre-cancerxe2x80x9d, Policlinico (Chrono)., 1995; 1: 23-30
Hayes, L et al., xe2x80x9cIncreased breast temperature in the xe2x80x98at riskxe2x80x99 breastxe2x80x9d, B. J. Cancer., 83, Supplement 1, 41, July 2000; also presented at the British Cancer Research Meeting, Jul. 9-12, 2000.
This invention is based on the observation that, in general, an increased risk of developing breast cancer later in life, pre-cancerous states of the breast and breast cancer may be recognized from accurate observations of breast surface temperatures using suitable apparatus and methods.
As hereinbefore noted, prior art thermometric breast assessment devices are in the form of sensors physically attached to the breast surface, brassieres with integral sensors or brassiere inserts which fit within, and which are retained by, the cups of a brassiere. Furthermore, with only one exception, all of those which we have been able to find are concerned with the detection of an actual cancerous lesion.
In marked contradistinction to prior art devices, the instant invention is neither physically attached to the breast surface and is also neither a brassiere nor a brassiere insert. Furthermore, it is primarily directed, by means of the function of its structural elements, towards the assessment and determination of the risk of developing cancer later in life by the measurement of breast temperatures, over a period normally of one and a half hours. Notwithstanding this, the instant invention may also be used to detect breast cancer and is useful in other areas, such as measuring the effect on breast temperatures of interventional strategies, including dietary strategies, in women at-risk, for instance those who carry genes associated with an increased breast cancer risk such as inter alia, BRCA1 and BRCA2.
In the original embodiment of the instant invention, a universal harness, only one size of which is needed to fit the great majority of subjects, comprises two flexible, flat, ring-like contactor pads, united anteriorly by a short, adjustable, elasticated strap and united posteriorly by a longer, adjustable and openable strap. The harness may be used in conjunction with the subject""s own brassiere or without a brassiere, according mainly to the choice of the investigator. Each contactor pad comprises substantially similarly sized and shaped inner and outer layers of flexible, compressible and extensible material which, conveniently, may be neoprene, provided with suitable flexible facing fabrics, such as the nylon material known commercially as Lycra(trademark).
Each contactor pad layer has two extension tabs, disposed about opposite ends of a diameter, for the attachment of the short anterior strap and the longer, openable, posterior strap. The contactor pad layers each have a central hole which is so sized that it will accommodate the areolar area of the majority of women and is conveniently about 50 mm in diameter. The outer diameter is conveniently about 100 mm. The inner and outer contactor pad layers are laid one over the other such that the extension tabs are aligned and are then stitched together around the circumference of the central hole.
An array of thermal sensors, preferably, but not necessarily, four in number, is disposed about the inner surface of the inner contact pad layer in a regular manner along the circular center line lying between the inner and outer boundaries. The sensors are preferably of the analog type which produce a current in proportion to temperature and are housed in a transistor can package. Each sensor of this type has three wire legs which are introduced through the material of the inner contactor pad layer. The neoprene material effectively self-seals against each sensor leg. The sensor cans are completely unsheathed, having no additional covering of any kind, in order to ensure contact with the breast surface and to maximize thermal transfer.
The three legs of each can package each engages a small disc-like molding, provided with through holes disposed, in its periphery, 120xc2x0 apart. The legs are then bent over at the periphery of the disc providing initial securing means for this assembly. Cable connecting means are in the form of light, flexible, plastics-sheathed outers each provided with a plurality of twisted pairs of inner cables, the number of pairs being the same as the number of sensors provided on each contactor pad. It is strongly preferred that a different color outer cable covering is used for each contactor ring and that a convention is adopted, during use, that the first color is always used with a first breast and that the second color is always used with a second breast. Wiring is accomplished according to a novel strategy directed towards ensuring that individual sensors are never subjected to traction in normal robust use.
Flexible insulating and cushioning means are introduced intimately about the sensor legs and connections and between the contactor pad layers which are then sewn together to complete the contactor pads. These are soft and compressible and have a xe2x80x98bulkedxe2x80x99 feel. The contactor pads are xe2x80x98handedxe2x80x99 and the sheathed outers of the cables are directed medially. A short, elastic, adjustable, anterior strap is sewn between medial tabs on each contactor pad. A longer elasticated, adjustable and openable posterior strap, is sewn to laterally directed tabs on each contactor pad.
The colored connecting cables terminate within the case of a monitor unit and preferably have a softness such that they drape readily under their own weight. This monitor is provided with electronic micro-circuitry which provides timing and memory means capable of polling each sensor, every sixty seconds, for one and a half hours and storing the data so collected. The sensors are, preferably, independently calibrated to within 0.01xc2x0 C. using pre-set potentiometer means located within the monitor unit. This is a much greater level of accuracy than prior art thermometric devices and is necessary to fulfill the purpose for which the apparatus is intended. The monitor is preferably powered by a rechargeable nickel hydride battery. The monitor is provided with a series of colored LEDs which indicate status of the system under a variety of conditions.
The temperature sensing cycle is initiated by depressing a plunger and the monitor unit switches off automatically at the end of the sensing cycle.
Data stored within the monitor is downloaded to a host PC, via an interface unit to which it is attached, with suitable connecting cable and plug means. The interface also provides charging means and this function is activated upon connection, whether the monitor is downloading or not. Conveniently, the interface will provide charging services for a plurality of monitor units, typically twelve at one time. The original disclosure called for a host PC, which preferably had a 100 MHz processor or better and used the Windows 95(trademark) operating system. However, it is in the nature of both processor development and operating system software development that they have been superseded by more powerful equivalents. The PC was to be provided with a dedicated program written, for instance, in Turbo-Pascal(trademark) for Windows(trademark), this program being capable, under keyboard or mouse command, of communicating with the monitor unit, initiating data download, capturing and saving downloaded data and displaying this in graphical and tabular form for each sensor. In addition the program provides means for pictorial graphic display of the temperature measured by each sensor, at each polling, displayed in its correct spatial position on each breast.
Re-setting the monitor unit for further use is normally carried out from Within the host computer, using software means, however, should there be a reason to abort a sensing cycle and start another, this is accomplished by depressing a re-start button mounted sub-flush with respect to the surface of the monitor case.
In use, the subject to be investigated, who will generally be between twenty and fifty years of age and, in any event, will not have reached the menopause, is counseled upon recruitment as to the nature of the test. Some time prior to the test, she is provided with a urine dip test kit which will indicate the day upon which she has a marked rise in luteinizing hormone. She is also provided with a series of sterile bottles in which to collect a series of at least three early morning saliva samples which, when the series is complete, are forwarded in the container provided, to a suitable laboratory equipped to carry out assays of salivary progesterone levels. These results are used to measure and predict the most suitable date in the subject""s next cycle to carry out the breast temperature test.
On the appropriate day, the subject is called to the location where the test is to be conducted. In a warm environment, where the ambient temperature should be 24xc2x0 C.xc2x12xc2x0 C., the subject is fitted with the harness of the instant invention. The subject may, in addition, wear her own brassiere if she wishes, or a sports type elasticated brassiere, or no brassiere. She should, however, wear a substantial and reasonably close-fitting over garment, to limit or prevent any generalized heat loss. It is essential that identification details relating to both the subject and the monitor unit are recorded together and that the integrity of this combined information is maintained. Only one size of the instant harness is normally provided and required.
The sheathed connecting leads between the harness and the monitor unit are led out from under the lower margin of the over garment. To start the test, the assistant, helper or other designated person depresses the plunger on the monitor unit, observing that the xe2x80x98startxe2x80x99 LED illuminates, to confirm initiation of the test. It will be found convenient if the subject is provided with a dressing gown in order that the monitor unit may be placed in a pocket during the test. Throughout the test period, the subject should be encouraged to sit quietly and avoid exertion and should not imbibe hot or stimulating liquids. At the end of one and a half hours, of which the first half hour is to allow that part of the apparatus in contact with the subject to equilibrate with the subject""s surface temperature, the test will be complete and the subject may return to a private cubicle to doff the harness and dress in her normal clothing prior to departure from the test center.
The data from the monitor unit used with the subject is downloaded into the computer, as hereinbefore described, and evaluated by a skilled trained person capable of comparing the subject""s breast temperature data with known norms with a view to reaching a conclusion concerning whether or not subject may be at risk of developing breast cancer at a future date.
In the event that this conclusion is positive, the subject would be informed promptly and invited back to participate first in a re-test and then in other tests. The purpose of these is to establish whether or not she may have existing cancer since, although the object of the test of the instant invention is not, primarily, to detect actual cancers, there will be some subjects who come forward who do have the undiagnosed condition. If she is negative to other tests for cancer, she will be informed that she is at a significant risk of developing breast cancer subsequently. This knowledge allows surveillance, prevention and future intervention strategies to be planned and implemented. These factors, in turn, improve the chances of preventing the disease or, should it prevail, successfully treating it at an early stage.
On the other hand, if the test is negative, the subject will also be so informed. In this event, the subject may well be reassured, however, she should be advised that she should return for retesting at a suitable interval which may be, say, two years. In any case, a follow up record and call-forward system should be maintained in order that any subjects which test negative can be called for a re-test after a suitable period.
The foregoing apparatus of the original embodiment of this invention underwent initial human trials at The European Institute of Oncology, Milan, Italy, according to a protocol which reflected the general method of use immediately hereinbefore described. These trials generally demonstrated that, in marked contradistinction to the Simpson and Green Chronobra(trademark) device, the novel harness and sensor arrangement is capable of producing a continuous reliable signal throughout a data collection period. The apparatus was also used in a few subjects prior to but on the same day that they were diagnosed with breast cancer by a xe2x80x98gold standardxe2x80x99 method, such as biopsy, and, in some of these, temperature xe2x80x98anomaliesxe2x80x99 were detected.
We have now made numerous improvements, which will be disclosed hereinafter, as a new and most preferred embodiment. The majority of our efforts have been directed towards non-obvious structural improvements with the intention of achieving enhanced reliability, durability, accuracy, acceptability for the test subject and service provider, effectiveness and security.
As in the original embodiment of the instant invention, a universal harness, only one size of which is needed to fit the majority of subjects, comprises two novel ring-like contactor pads. However, we now prefer not to unite the contactor pads anteriorly with direct means. The harness may be used in conjunction with the subject""s own brassiere or without a brassiere, according mainly to the choice of the investigator.
Improved harness means includes improved contactor pads, each including a thin flexible printed circuit board (PCB) manufactured flat as a ribbon and having an overall shape somewhat reminiscent of a large inverted question mark with an extended tail. It is to be understood that in the improved harness, one design of PCB may be used by adopting both a right and a left orientation. A first portion forms, substantially, an incomplete circle, the inner margin of which, in the flat condition, largely encloses a circular area; a second portion, continuous with the first portion, is curved and extends over some 90xc2x0 of arc; and a third portion, continuous with the second portion, is substantially straight to form a lead and extends to a second end.
A plurality of novel integral flexible primary tabs is provided about the inner margin of the first circular portion of the ribbon PCB, preferably but not necessarily disposed at intervals of 60xc2x0 and which extend radially and inwardly. A further plurality of similar integral primary tabs may, optionally, be disposed about the greater part of the outer margin of the first circular portion of the ribbon PCB.
The ribbon PCB carries electrical connection means in the form of insulated copper tracks, adapted by the provision of suitable perforations, on each primary tab, to provide reception and mounting means for surface mounting thermal sensor means. Perforated reception and mounting means are adapted in such a manner as to allow thermal sensor means to be mounted on either side of the primary tabs.
A plurality of integral secondary tabs is provided, extending radially inwardly and outwardly, in pairs, at convenient positions around the first circular portion of the ribbon PCB. One pair of secondary tabs is preferably disposed near the top of the xe2x80x98question mark shapedxe2x80x99 ribbon PCB and a second pair is preferably disposed at that point where the first circular portion of the ribbon PCB adjoins the second curved portion.
All the secondary tabs are reinforced and also adapted by the provision of fold lines in the ribbon PCB material to allow them to each be formed into an outwardly directed flap. Each pair of secondary tabs is further adapted by the provision of one in each pair with a self-adhesive pad of hook closure material and the other with a pad of loop closure material in a corresponding desired position such that, when the flap formed by each secondary tab of one pair is folded and closure is effected, receiving means is formed for the releasable and slidable receival of body strap elements of the harness.
Each of the secondary tabs forming that pair positioned adjacent the second curved portion of the ribbon PCB, is further adapted in regions close to their origins from the inner and outer margins of the ribbon PCB by the provision of fixing means, conveniently in the form of soldering points exposed on both sides and incorporated at the time of manufacture. Similar fixing means are provided on small extensions formed on the inner and outer margins of the first end of the ribbon PCB. During assembly, soldering points located on the inner and outer margins of the first end of the first portion of the ribbon PCB and corresponding soldering points located on the inner and outer secondary tabs are drawn into apposition and wire and solder joints made, thereby forming a flexible annulus which is also, substantially, a frustum of a cone.
By drawing the soldering points located on the front aspect of the first end of the first ribbon PCB into apposition with those located on the rear aspect of the secondary tabs, the frustum will be formed in such a manner as to provide a novel accommodating structure for a left breast. Conversely, by drawing the soldering points located on the rear aspect of the first end of the second ribbon PCB into apposition with those located on the front aspect of the secondary tabs, the frustum will be formed in such a manner as to provide an accommodating structure for a right breast. Two of these structures may be combined in a compound structure which, with suitable cleanable, permanent covering means, forms a pair of contactor pads suitable for accommodating a pair of human female breasts.
Each primary tab is provided with a thin layer of closed cell foam of similar size and shape, adhesively applied on both aspects to prevent heat loss and damage to the covers from soldering points.
Body strap elements of the harness comprise multiple elasticated strapping elements which include releasable attachment and adjustment means for attachment to the human female body in the breast area. In particular, two transverse anterior straps are joined at both ends and at each end to a posterior strap forming a xe2x80x98Yxe2x80x99 configuration with an enclosed angle conveniently of about 40xc2x0. A short vertical anterior elasticated strap is non-releasably secured centrally and at right angles to one transverse anterior elasticated strap and releasably and adjustably to the other.
The relationship between the body strap elements of the harness and the flexible contactor pad elements is important and the width of the transverse anterior elasticated straps is selected so that the latter may be readily and releasably engaged, in a slidable manner, with the folded flap closures formed by the secondary tabs on the contactor pads. Fundamentally precise positioning of each contactor pad over each breast, concentric with the nipple, is possible partly by virtue of the provision of the second curved portion of the ribbon PCB and partly due to the fact that the contactor pads may be freely located with respect to one another over any rational range. The dispositions on the first circular portion of the ribbon PCB of the secondary tabs forming securing means for the transverse anterior straps and the geometry of the mutual permanent attachments between these straps are selected to optimize contact between the contactor pads and the subjects breasts. The short vertical anterior strap provides further adjustment directed towards optimizing pad-to-breast contact, particularly on the medial aspects, by allowing the transverse anterior straps to be gently drawn towards one another in the central area between the breasts. Both the contactor pad sub-assemblies and the body strap elements are intended to provide a one-size-fits-all solution for the great majority of the population, however, it is recognized that there will be a need for a low use variant for extremely large subjects and another for extremely small subjects. This is a significant improvement over prior art systems which depend upon a multiplicity of sizes of brassiere or brassiere inserts.
However, more important than any of these factors is the provision of the primary tabs for sensor mounting. These are so sized and shaped that, whatever breast size or shape the first circular portion of the ribbon PCB is drawn against, with the breasts protruding through the flexible frustum structure, primary tabs will tend to be splayed gently but firmly into compressive contact with the breast surface.
We now prefer to use seven sensors in each array, preferably six sensors disposed symmetrically on primary tabs on the inner margin of each contactor pad and one further sensor disposed on the outer margin on a primary tab directed towards the axilla. We prefer a precision temperature monitor integrated circuit of analog type which produces a current in proportion to temperature though there are now available temperature-voltage based types which could be used with little difference in performance in general use. All primary tabs are provided with second exposed grouped multiple soldering points, which constitute bridging wiring connection means for most preferred sensor means and also connection means for micro-miniature trimming components and bridging wiring connection means for alternate versions of this most preferred embodiment which employ temperature-voltage based type sensors.
The most preferred sensor has cylindrical, flanged, metal can package with a flat-topped upper surface having a curved periphery. Each sensor has three stiff wire legs for engagement with a thin plastics insulating spacer washer and perforated soldering points on primary tabs. The plastics washer prevents any risk of short circuiting the metal can on the soldering points and raises the exposed profile of the sensor above the cover of the PCB. The functional surfaces of sensors are used unsheathed, in order to ensure intimate contact with the breast surface and to maximize thermal transfer. Each sensor is individually resistance calibrated to xc2x10.01xc2x0 C.
Thin closed cell foam layers cover both sides of each primary tab. Those on the sensor mounting side have a die cut substantially circular hole which registers with and passes over the flange of the can package so that it fits intimately over the plastics disk washer. A circular die cut hole in the cover fits intimately around the cylindrical body portion of the metal can package and also lies intimately above and upon the flange. On that side of each primary tab facing away from the breast, the primary function of the closed cell foam layer is to prevent radiant and conductive heat loss from the primary tab and, most especially, from the associated sensor and the secondary function of mitigating the potential for any residual solder nibs or trimmed wire ends to abrade or pierce the cover.
On the breast facing side, the primary function of the closed cell foam layer is to prevent any damage residual solder nibs or trimmed wire ends and to prevent any undesirable breast contact with these.
The secondary function is prevention of heat loss and this is important because, if the closed cell foam layer were not interposed between the cover and the PCB, the proximity of copper tracking within the PCB could lead to undesirable lateral conductive heat loss. This would be unacceptable in the context of an apparatus intended to measure temperature differences to xc2x10.01xc2x0 C.
It will now be appreciated that, in this improved version of the harness of the instant invention, we have disclosed structural and functional improvements, eliminated a number of components and numerous manufacturing steps and, additionally, the weight has been reduced. Furthermore, the drape characteristics of covered ribbon PCBs are considerably improved when compared to the sheathed cables of the original embodiment, which each carry eight twisted wire pairs, and advantage is taken of this in the straight portions of the ribbon which constitute connection leads to a data-logger.
Data-logging means are provided in the form of a data-logger having significantly improved functionality, safety and security over that which we disclosed in the original embodiment of the instant invention as a monitor unit. An exposed area near the second end of the PCB is adapted in each case by the provision of discrete exposed soldering points. This portion of the two PCBs is each received, respectively, into the data-logger where they are provided with both mechanical securing means and electrical connection means preferably in the form of permanently soldered connections. The data-logger is lightweight and has a substantially oblong plastics case, and preferably is worn suspended from the neck of a subject on a light adjustable strap having quick release connection means.
The data-logger, which provides significantly improved functionality, safety and security over the monitor unit disclosed in the original embodiment of the instant invention, is provided with electronic microcircuitry based around a microprocessor which is used to control data collection, storage and subsequent downloading of recorded data to the host PC. The data-logger is a sixteen-channel device, of which fourteen channels are used to monitor outputs from each sensor comprising the two seven-sensor left and right breast sensor arrays. Two channels are used to confirm the integrity of harness. The data-logger is provided with clock timing means and the processor is capable of polling every sensor at selected intervals for periods of up to seven days. Individual sensors are each calibrated to xc2x10.01xc2x0 C. at the time of manufacture of the data-logger by adjusting the calibration resistance. This high level of accuracy, which is not found in the prior art, is essential in this apparatus in order to fulfill the purpose of breast thermometry testing in the context of breast cancer risk and breast cancer. Each of the sensors is polled in rapid sequence, using analog multiplexers. Each of the sensor readings is fed into an operational amplifier, which conditions the signal so that it can be processed. This is achieved by converting the analog signal into a digital one using an analog to digital converter. Once in digital form, the data from a set of readings are stored in non-volatile flash memory until the microprocessor is instructed to upload data to the host PC. The operations of writing and addressing, the duration of the readings, as well as the time between readings, are all controlled by the microprocessor. The data-logger is powered using rechargeable batteries. Separate voltage levels are used for the analog and digital parts of the circuit in order to reduce interference and these are controlled using regulator chips to maintain correct values. A separate control amplifier is provided to monitor an ambient temperature sensor mounted on the data-logger case. A further separate control amplifier is provided to monitor an additional sensor used to measure a non-breast body surface reference temperature and attached to the data-logger by a flying lead.
The data-logger is provided with display means in the form of light emitting diodes (LED) which indicate xe2x80x98power onxe2x80x99, xe2x80x98thermometric test runningxe2x80x99 and xe2x80x98low battery statusxe2x80x99, respectively. Further display means are conveniently in the form of a multi-line, multi character, liquid crystal display (LCD) which indicates electrical status of the data-logger and harness under a variety of conditions and also shows test-critical and test subject security data, including unique test subject identifiers. Push button switches control xe2x80x98power on/offxe2x80x99, xe2x80x98function displayxe2x80x99 and xe2x80x98test initiationxe2x80x99, respectively. Provided that the data-logger has been brought to readiness according to a carefully controlled protocol, a temperature sensing cycle can be initiated by pressing the xe2x80x98test initiationxe2x80x99 button. The data-logger switches off automatically at the end of a sensing cycle.
Interaction between the data-logger and the host PC is managed with serial interface means integral with the host PC and in the form of an internal PC card which includes a single upload/download data port. The interface also has multiple charging ports for the automatic battery charging of data-loggers attached to it.
At an appropriate time, stored data within the non-volatile flash memory are uploaded to the host PC via the upload/download data port. After uploading data from any particular subject and until the download of security data from the PC to the data-logger for the next test, the LCD display shows the subject name and test number from the last performed test. Other information can be read from LCD display by toggling the xe2x80x98function displayxe2x80x99 button and by noting the condition of LEDs.
The host PC includes an entry level motherboard and microprocessor, or better, suitable operating system and a dedicated software program. Commands which control the flow of data to the host PC are set from the keyboard and mouse of the host PC and sent to the microprocessor of the data-logger via the upload/download data port. Data are date-stamped using an internal real time clock (RTC) within the data-logger. System variables, such as test period and time between sensor readings, are set and downloaded in a similar manner and new values are stored in the non-volatile flash memory of the data-logger for controlling subsequent test parameters. PC software is protected by a hardware security device which, if not connected to the host PC, will prevent all operational access. The security device may, optionally, incorporate means for integrating a credit system for levying a monetary charge for each test.
Access to the dedicated software program is subject to multi-level password access and also time-out control and all operators are required to log a unique password, and then other suitable unique identifier details, such as name, status and, if applicable, employee number, to a designated field displayed on an opening screen on the VDU of the host PC. Access will time-out at a predetermined time at the end of each work day unless temporarily defeated by a task in progress, following the completion of which, access time out will prevail so that if continued access is required it will be necessary for operators to log on once more, thus ensuring that any out-of-hours access is logged to the system. Time out occurs, in any event, at midnight each day.
The dedicated software program provides improved screen data displays and these range from the simple numerical display of temperature data in spreadsheet style to elaborated graphics. All displays follow an informal international standard used by surgeons to reference landmarks on the human breast. This involves representation of the breast from a xe2x80x98within-subjectxe2x80x99 viewpoint and then addressing first the upper outer quadrant and proceeding clockwise to the upper inner quadrant.
Since the disclosure of the original embodiment of the instant invention, we have gained a much fuller appreciation of the importance of providing women with better and earlier information on their breast health status. Furthermore, we have encountered press reports of occasional, but disastrous, examples of patient records which have become mixed up, leading to inappropriate surgery or non-diagnosis. We also now know that other important applications include monitoring responses to dietary and other intervention strategies for high risk women, improving the quality of counseling to those considering prophylactic mastectomy and optimizing the time of surgery in very large tumors.
These additional uses support the use of a greater number of sensors in each breast sensor array. However, the primary use of the new and improved embodiment is the assessment of risk in subjects, who appear to be generally healthy, of developing breast cancer later in life. In this large group of women the aim is to collect temperature data generated by a general physiological response to the tidal hormonal flow throughout the menstrual cyde, at a particular point in that cycle. On this basis it would seem that there is no need to collect data from any specific point or points on the breast. However, breast cancer is highly prevalent in the subject population and it is not possible to tell, in advance, whether any given subject, presenting for routine risk assessment, may actually be harboring breast cancer. In mass applications of the instant invention, this scenario will be quite common and there is an implicit duty of care upon any service provider to collect not only general indicative data but also more specific data which may help to localize a lesion, if present.
The method of use of the harness and data-logger of the new and most preferred embodiment will usually be the same, regardless of the application. In the primary application the approach is also, in general, similar to that employed with the original embodiment. In the new applications, the use of serial progesterone assays may or may not be used to determine a specific test day. Where progesterone assays are used, they will be substantially the same as those used in conjunction with the original embodiment.
At any test location, on any test day, for any application of the new and improved embodiment of the improved instant system, authorized operators both of the host PC and data-loggers must log on to the host PC system by entering passwords and identifier details. Access will time-out at a pre-determined time at the end of each work day. A strict protocol involving the input of mandatory entries, concerning the subject, to a new subject record which has a unique alpha numeric identifier must be followed before the host PC can generate a unique test number and then ready a data-logger for use. Providing the data-logger holds no data and has an adequate power reserve, it will be readied for use and the test number, subject surname and first name appear on data-logger LCD display until any upload of collected data. The data-logger will time out if the test is not started within a pre-set time. System variables, including test parameters, may only be varied by an authorized person, such as system engineer, having a higher level of password controlled access.
In a room maintained at 22xc2x0 C.xc2x12xc2x0 C., a female helper who is also the data-logger operator assists the subject who doffs her upper garments in privacy. The subject must confirm her first name and surname verbally and must check the spelling of both her names by inspection of the data-logger LCD display. In the event of any discrepancy, the data-logger must not be used until the error has been corrected. This involves postponing the test and readying the data-logger once more. If the subject identity confirmation procedure is not followed, and more than one subject is present at the test location, the entire security of the system could be compromised.
The data-logger is suspended from the neck of the subject on light adjustable strap. The breast accommodating structures of the contactor pads and the body strap assembly are then fitted on to the subject and adjusted so that each contactor pad is located concentrically about a nipple and the primary tabs are splayed into gentle compressive contact with the surfaces of the breasts. It should be noted that, as with the original embodiment, the subject may wear her own brassiere, or a sports type elasticated brassiere, or no brassiere according to her wishes and the professional guidance of the operator helper. It is important that the subject wears a substantial and reasonably close fitting over-garment to limit or prevent any generalized heat loss and the data-logger rests outside this, adjusted so that it rests in a position of comfort on the upper chest just above the breasts. The operator helper depresses the test initiation switch on the data-logger to initiate the test cycle. Subject data collection commences, automatically, after a thirty minute period for temperature equilibration between the subject and the harness. Ambient and body reference temperatures are monitored during the test. At the end of a test period, the data-logger LCD displays the message test finishedxe2x80x94upload data. The subject may now doff the over-garment and harness, dress in her normal clothing and leave the test location.
The data-logger and permanently attached harness are returned to the host PC and connected both to the charging port and the data-port, which initiates a diagnostic test on the integrity of the data connection. If the connection is satisfactory, the host PC automatically interrogates the data-logger to identify the test number, uses this to identify the subject record, which is in turn used to open the associated file to which test data are automatically uploaded from the data-logger. Once uploading is complete, the host PC erases the data-logger memory.
Subject test data is evaluated by a person suitably skilled and trained to interpret it and reach conclusions concerning the breast status of subjects. These may vary according to the specific purpose for which the collected data is intended to be used. If the subject requires further investigation, treatment or follow up, she is informed promptly, possibly on the day the test is carried out, especially when strategies need to be implemented urgently. Further investigation may well involve an early retest with the instant system, as well as other tests, to confirm whether or not she may have existing cancer, or the extent of existing cancer, or the optimal time for surgery. It is statistically likely that if the instant test is deployed on a large scale for the assessment of breast cancer risk, the subject population will include women who have the undiagnosed condition. Even when test results indicate no cause for significant concern, this information is desirably communicated to subjects as quickly as possible in order to alleviate or prevent any unnecessary stress. The dedicated program of the host PC incorporates an automatic review and call-back routine by default with interval period parameters constituting one of the system variables.
It will be appreciated that the stringent password and personal identifier security measures introduced in the new and improved embodiment of the instant invention ensure that all reasonable measures have been taken to provide an audit trail for responsibility for data collection, management and interpretation in this potentially life-critical mass screening test.
Accordingly it is a first object of the present invention to provide apparatus capable of making accurate measurements of temperatures on the surface of the human breast, particularly the female breast;
It is a second important object of the present invention to reliably record and store measurements of temperatures on the surface of the human breast;
It is a third important object of the present invention to manipulate and display temperature data collected from the surface of the human breast;
It is a fourth important object of the present invention to provide a method for the assessment of the risk of subsequent development of breast cancer in women who do not currently have the disease;
It is yet another object of the present invention to provide a method for the detection of breast cancer in women;
It is yet another object of the present invention to provide a method for monitoring the effect of intervention strategies on women who have been diagnosed as being at an increased risk of developing breast cancer;
It is yet another object of the present invention to provide apparatus for monitoring a second breast in women who have undergone mastectomy of a first breast for breast cancer.
It is yet another object of the present invention to provide a method for improving the quality of counseling to women considering prophylactic mastectomy of a second and apparently unaffected breast.
It is yet another object of the present invention to provide apparatus for monitoring the breast of a woman with a very large tumor with a view to optimizing the time of intended surgery and for assessing surgical outcomes.